STUDIES ON THE PHOTO‐C4‐CYCLO‐ADDITION REACTIONS BETWEEN SKIN‐PHOTOSENSITIZING FUROCOUMARINS AND NUCLEIC ACIDS*

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Abstract
Abstract— Among the natural or synthetic furocoumarins (psoralens) a group exists which has interesting biological properties, the best known of which is skin‐photosensitization. The mechanism of action has remained unclarified for a long time. Furocoumarins lack photooxidative properties; they act by a mechanism that does not require oxygen and are therefore different from photodynamic substances. Photosensitizing furocoumarins when irradiated at 365 nm react with nucleic acids to give a C4‐cyclo‐addition to the 5,6‐double bond of the pyrimidine bases engaging their 3,4‐ or 4‵,5‵‐double bond. Differences exist in the behaviour of the various furocoumarins; psoralen reacts equally well with native DNA, with denatured DNA and with RNA, whereas bergapten, xanthotoxin and 8‐methylpsoralen at room temperature react to a much greater extent with native DNA than with denatured DNA and with RNA. A temperature effect has also been observed. In the case of native DNA an intercalation, occurring in the dark, of furocoumarins between two adjacent base pairs of the double helix is suggested as the first step in the reaction. The photoreaction is not accompanied by breaks in the polynucleotide chain or by conformational modifications of the macromolecule. A parallelism was observed between the order of activity of the substances of this group for photoreaction with native DNA and for skin‐photosensitization. Ehrlich ascites tumor cells lose completely their capacity of transmitting the tumor after irradiation in the presence of psoralen, bergapten and xanthotoxin. By hydrolysis of DNA extracted from Ehrlich ascites tumor cells irradiated in the presence of psoralen a photoadduct between psoralen and thymine was isolated.